Tesche F, Miosge N
Zentrum Anatomie, Abteilung Histologie, Kreuzbergring 36, 37075 Göttingen, Germany.
Osteoarthritis Cartilage. 2004 Nov;12(11):852-62. doi: 10.1016/j.joca.2004.07.004.
Disturbances of the proteoglycan metabolism play an essential role in the pathology of osteoarthritis. The extracellular matrix proteoglycan, perlecan, has lately been identified as a cell biological factor in cartilage development and maintenance. We investigated the tissue distribution of perlecan, the relation between the level of the protein and its mRNA and which type of cell, type 1 chondrocytes or elongated secretory type 2 cells, produces perlecan in late stages of osteoarthritis.
In 10 patients suffering from late-stage osteoarthritis tissue samples taken from a macroscopically intact area and the area adjacent to the main cartilage defect were investigated. We performed quantitative immunogold histochemistry and in situ hybridization in vivo and determined the level of perlecan mRNA with the help of real-time RT-PCR in native cartilage tissue and in cultured cells.
In vivo, an increased level of perlecan protein was found in the area adjacent to the main defect. A 45% rise in the level of perlecan mRNA secreted by elongated secretory type 2 cells in comparison to type 1 chondrocytes was detected. Type 2 cells also translated the highest levels of perlecan to be deposited mainly in the pericellular matrix, and also in the interterritorial matrix in late stages of osteoarthritis. Also in vitro, type 2 cells showed a 50% higher level of mRNA for perlecan.
We found evidence that perlecan is involved in the pathogenesis of late stages of osteoarthritis. The levels of perlecan protein and mRNA are up-regulated especially by the elongated secretory type 2 cells in the area adjacent to the main cartilage defect. This might be seen as an attempt on the part of the cartilage tissue to stabilize the extracellular matrix.
蛋白聚糖代谢紊乱在骨关节炎的病理过程中起重要作用。细胞外基质蛋白聚糖，基底膜聚糖，最近已被确定为软骨发育和维持中的一种细胞生物学因子。我们研究了基底膜聚糖的组织分布、蛋白质水平与其mRNA水平之间的关系，以及在骨关节炎晚期哪种类型的细胞，即1型软骨细胞或细长分泌型2型细胞产生基底膜聚糖。
对10例晚期骨关节炎患者取自宏观上完整区域以及与主要软骨缺损相邻区域的组织样本进行研究。我们在体内进行了定量免疫金组织化学和原位杂交，并借助实时逆转录聚合酶链反应在天然软骨组织和培养细胞中测定基底膜聚糖mRNA的水平。
在体内，在主要缺损相邻区域发现基底膜聚糖蛋白水平升高。检测到细长分泌型2型细胞分泌的基底膜聚糖mRNA水平比1型软骨细胞高45%。在骨关节炎晚期，2型细胞还将最高水平的基底膜聚糖翻译出来，主要沉积在细胞周围基质中，也沉积在区域间基质中。在体外，2型细胞的基底膜聚糖mRNA水平也高出50%。
我们发现证据表明基底膜聚糖参与骨关节炎晚期的发病机制。基底膜聚糖蛋白和mRNA水平尤其在主要软骨缺损相邻区域被细长分泌型2型细胞上调。这可能被视为软骨组织试图稳定细胞外基质的一种尝试。
